Hyperlipoproteinemia associated with elevated very low density lipoproteins (VLDL) and/or chylomicrons (chylo) is the most common form of hyperlipidemia in our population. The underlying mechanisms responsible for hypertriglyceridemia have been suggested to be the overproduction and/or defective removal of triglyceride-rich lipoproteins (TRL). A greatly increased production of VLDL without significant hypertriglyceridemia in obese patients indicates that defective removal or degradation of TRL might be the predominant mechanism. Lipoprotein lipase (LpL) is the key enzyme that mediates the hydrolysis of circulating TRL. The post heparin LpL activity in many hypertriglyceridemic subjects has been reported to be normal even though the level of VLDL or chylo is greatly elevated. In initial studies, taking advantaged of the rapidity and resolution of single vertical spin ultracentrifugation, we have demonstrated significant differences in the kinetics of in vitro lipolysis of plasma from normaolipidemic versus hyperlipidemic subjects; VLDL from both type IV and type III subjects has been shown to be defective as a LPL substrate. The objectives of this proposal are to contiue our studi of the roles of LPL and hepatic lipase (HL) in the interconversion of TRL in normolipidemic and hypertriglyceridemic plasma. The efficiency of VLDL and chylomiocrons obtained from various types of hyperlipoproteinemia as LPL or HL substrates and the ability of various plasma lipoprotein and free protein fractions as acceptors of lipolytic products will be examined and related to composition and structure. In vitro produced lipolytic products of TRL core (remnant particles) will be interacted with arterial smooth muscle cells in culture, and the ability of these remnants to deliver cholesterol to cells will be compared with control lipoproteins. As a long term goal, rabbits will be placed on an atherogenic diet, and the change in post heparin LpL and HL activity, in reactivity of TRL to LpL and HL and in ability of various plasma fractions to support lipolysis will be examined. Findings from these studies should provide information related to the biochemical defect of hypertriglyceridemia and may ultimately prove relevant to its treatment and management.